PET-MR: Challenges and New Directions

Key Points

• The combination of PET and MR technology is highly complementary.

• The issue of accurate MR-based methods for attenuation correction of the measured PET data needs to be

addressed.

• PET-MR imaging is clinically indicated for certain paediatric cancers, lymphoma, breast and prostate cancers and head and neck tumours, with the benefit of reduced radiation exposure. Future applications may include imaging the brain for Alzheimer’s disease.

• Few clinical studies are published, but several show a better performance in indications requiring high soft tissue contrast.

• Use of quantitative measurements of tracer uptake is preferable to visual assessment in determining accurately and objectively the degree of tumour response.

The combination of clinical
MR and PET scanners has received increasing attention in recent years. The information
provided by MR enables PET-MR to go far beyond simple anatomical registration
of PET molecular imaging, while the simultaneous acquisition of PET and MR data
opens up new opportunities impossible to realise using sequentially acquired
data. This combination of MR and PET technology has proven to be very challenging
due to the detrimental effect of the scanners on each other’s performance. Significant
progress has been made in the last 10 years to solve various technical issues,
leading to the recent release of clinical whole- body hybrid scanners.

Technical Aspects

As PET lacks the spatial
resolution offered by MRI, which in turn lacks sensitivity, the combination of
PET and MR technology is highly complementary. While PET-CT scanners have
quickly been integrated into clinical routine, the development of combined PET
and MR has been much slower, because of numerous technical challenges on both
sides (Catana et al. 2013). MR cannot simply replace the CT part of a PET-CT
scanner, as a whole-body PET-MR system requires technical modifications of both
the PET and MR part. Details of the physics of these challenges (Quick 2014)
are beyond the scope of this article. One major challenge of PET technology in
an MR environment is the presence of a magnetic field causing spatial
distortion in photomultiplier tubes (PMT), which are the scintillation light
detectors for PET scanners. Advances in photondetector technology have led to
silicon- PMTs, which are insensitive to magnetic fields.

PET, on the other hand, can
be challenging for MR technology (image artefacts or decreased signal-to-noise
ratio, susceptibility effects etc.). Moreover, the issue of accurate MR-based
methods for attenuation correction of the measured PET data, particularly
important for quantitative PET, needs to be addressed. Different methods for
deriving attenuation maps from MR have been proposed (Catana et al. 2013; Pace
et al. 2013). One of the main challenges, i.e. the limited space available
inside the bore of standard MR systems, has been solved by introducing larger,
70 cm bore diameters providing enough space to integrate the PET camera (Catana
et al. 2013).

PET-MR Scanners for Clinical Use

Following the installation
of the first head-only PET-MR scanner in 2007 (Schlemmer et al. 2008), whole-body
PET-MR scanners have been introduced into clinical routine by the major medical
equipment manufacturers (Siemens Healthcare, Philips Healthcare, GE
Healthcare), proposing different PET-MR designs. As only a few whole-body
PET-MR systems are already operating, the challenge is to understand the
clinical potential of this new imaging modality. Although still limited in
numbers, several studies show a better performance in those indications requiring
high soft tissue contrast.

Clinical Applications

Whole-body PET-MR imaging has
the potential to supplement or even replace combined PET-CT imaging in selected
clinical indications. When discussing the immediate benefits of combined PET-CT
examinations, the issue of patient exposure must be taken into account. As
shown in a multicentre study, whole-body PET-CT examinations result in an
effective dose to patients in the order of 25 mSv, and thus mandate a thorough
medical justification for each individual patient. Up to 70% of the total
radiation exposure is contributed by CT (Brix et al. 2005). It would thus be
very welcome if PET-MR could replace PET-CT whenever possible, as soon as the methodological
challenges of this new imaging modality have been overcome.

In various paediatric
malignancies PET-CT has significantly improved diagnostic accuracy. However,
due to the increasing consideration of radiation risk, especially to the paediatric
population, prospective studies are limited, because whenever a PET scan is
needed in these patients a CT scan is also required for attenuation correction or
for anatomical correlation. MR in PET-MR scanners could replace CT for
attenuation correction in these patients, thereby
significantly reducing radiation exposure compared to
a PET-CT study (Catana et al. 2013).

In
patients with head and neck malignancies, MR is superior to CT in terms of
accurate staging of tumour extent, involvement of soft tissue structures and
nodal involvement. Therefore, PET-MR will likely improve the assessment of
tumour extent, involvement of bony structures and bone marrow (Catana et al.
2013).

MR is
also the modality of choice to assess and stage prostate cancer. It can
reliably diagnose extracapsular extent and neural invasion (see Figure 1) and
can improve the accuracy of the assessment of the primary tumour (Jambor et al.
2012; Beer et al. 2011).

In
breast cancer MR has been shown to be very useful for local staging and
treatment monitoring, and it has greater sensitivity even than conventional
imaging methods. Currently, there is insufficient data from larger patient cohorts
available regarding the performance of combined PET-MR in imaging primary
breast cancer and determining local tumour extent. Initial experience with a
combined PET-MR approach for the evaluation of the primary tumour suggests that
adding FDG-PET information to MR mammography leads to improved information
regarding local tumour extent (Buchbender et al. 2014; Pace et al. 2014).

PET/CT
is increasingly used for monitoring the ef fectiveness of therapy in patients
with malignant diseases. Use of quantitative measurements of tracer uptake is preferable
to use of visual assessment in determining accurately and objectively the
degree of tumour response. Combined PET/MR measurements could help quantify precisely
how tumour vascular properties (assessed by functional MR methods),
proliferation and anti-tumour effects (assessed with PET) occur and interact
(Catana et al. 2013) (see Figure 2).

A
future application where PET-MR may change how we practice is to assess
patients with suspected Alzheimer’s disease (AD). The combination of PET and MR
imaging will lead to an earlier and more definitive diagnosis as PET and MR
provide complementary information (Jack 2008): PET can characterise local
upload of amyloid, whereas MR depicts neuronal degeneration.

Costs and
Reimbursement

The
applicability and recognition of PET-MR as an imaging modality in diagnostic
oncology is affected by several factors, of which reimbursement seems to be a
major obstacle for the diffusion of PET-MR in a clinical setting. Comparative
clinical benefits for existing PET-MR approaches need to be established, as
well as the caseload and case mix required for effective utilisation of a
hybrid PET-MR-scanner. PET-MR has developed and matured over the last decade.
The technology's cost remains a significant obstacle. Integrated PET-MR
scanners carry a price tag of approximately US $7 million. Similar to PET-CT
scanners, which were very expensive when they first came out, and dropped in
price as the technology became more available, PET-MR-scanners will also
decline in price. More research is needed to determine the cost effectiveness
of PET-MR technology (Goyen 2014).

Conclusion

PET-MR is an exciting imaging technology with great potential, paving
the way for increased diagnostic power in several clinical scenarios, but the
main indication for PET-MR in oncology remains to be defined. PET-MR definitely
has the potential to significantly increase our knowledge in vivo of cancer
physiology. Many factors will decide the ultimate role of PET-MR systems within
the overall healthcare system, not the least of which is the cost of such
systems, and the degree to which the benefits accrued match the resources required
to perform and interpret these studies in the clinic, as PET-MR will demand
interdisciplinary training and a truly multidisciplinary set up involving
physicians, physicists and technologist from both the field of nuclear medicine
and PET as well as MR imaging and radiation therapy (Catana et al. 2013). If
the future of clinical practice is precision medicine, where therapeutic
decisions are designed around specific molecular pathological events at the
earliest possible stage (Goyen 2014), then PET-MR systems will dramatically
impact the expanding field of molecular imaging in the future.